The tumor-inhibitory effectiveness of a novel anti-Trop2 Fab conjugate in pancreatic cancer.
The tumor-inhibitory effectiveness of a novel anti-Trop2 Fab conjugate in pancreatic cancer.
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DOI：
10.18632/oncotarget.8529
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发表时间：
2016-04-26
期刊：
影响因子：
--
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Mao Y;Wang X;Zheng F;Wang C;Tang Q;Tang X;Xu N;Zhang H;Zhang D;Xiong L;Liang J;Zhu J
人类滋养层细胞表面抗原2（Trop 2）已被报道致癌作用。本研究采用一步法实时定量聚合酶链反应（qPCR）和免疫组化（IHC）方法，探讨Trop 2表达与PC临床病理特征的关系。然后将新型抗Trop 2 Fab抗体与多柔比星（DOX）缀合以形成抗体-药物缀合物Trop 2Fab-DOX。通过细胞ELISA和免疫荧光测定来表征该Trop 2Fab-DOX缀合物。采用MTT法和伤口愈合实验检测Trop 2Fab-DOX对PC细胞的体外生长抑制作用，建立裸鼠移植瘤模型检测PC的体内抑瘤作用。在PC组织中观察到高Trop 2表达，Trop 2表达与PC患者的几个恶性属性相关，包括总生存期。Trop 2Fab-DOX可以与表达Trop 2的PC细胞结合，并提供改善的DOX释放类型。此外，Trop 2Fab-DOX在体外呈剂量依赖性抑制PC细胞增殖和迁移，在体内则抑制PC移植瘤生长。Trop 2是PC的特异性标志物，新型Trop 2Fab-DOX ADC具有有效的抗肿瘤活性
Human trophoblastic cell surface antigen 2 (Trop2) has been reported to act oncogenically. In this study, one-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis with were employed to evaluate the relationship between Trop2 expression and the clinicopathological features of patients with PC. Then a novel anti-Trop2 Fab antibody was conjugated with Doxorubicin (DOX) to form Trop2Fab-DOX, an antibody-drug conjugate. This Trop2Fab-DOX conjugate was characterized by cell ELISA and immunofluorescence assay. MTT and wound healing analyses were used to evaluate the inhibitory effect of Trop2Fab-DOX on PC cell growth in vitro, while xenograft nude mice model was established to examine the tumor-inhibitory effects of PC in vivo. High Trop2 expression was observed in PC tissues and Trop2 expression was associated with several malignant attributes of PC patients, including overall survival. Trop2Fab-DOX can bind to the Trop2-expressing PC cells and provide an improved releasing type of DOX. In addition, Trop2Fab-DOX inhibited the proliferation and suppressed the migration of PC cells in a dose-dependent manner in vitro, while inhibited the growth of PC xenografts in vivo. Trop2 is a specific marker for PC, and a novel Trop2Fab-DOX ADC has a potent antitumor activity
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影响因子：
4.6
作者：
Gu X;Fu M;Ge Z;Zhan F;Ding Y;Ni H;Zhang W;Zhu Y;Tang X;Xiong L;Li J;Qiu L;Mao Y;Zhu J
通讯作者：
Zhu J
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影响因子：
2.8
作者：
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通讯作者：
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影响因子：
3.7
作者：
Chen X;Ding G;Gao Q;Sun J;Zhang Q;Du L;Qiu Z;Wang C;Zheng F;Sun B;Ni J;Feng Z;Zhu J
通讯作者：
Zhu J
影响因子：
2.8
作者：
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通讯作者：
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影响因子：
10.8
作者：
Etrych, Tomas;Mrkvan, Tomas;Ulbrich, Karel
通讯作者：
Ulbrich, Karel